The objective of our research program is to conduct an integrated multidisciplinary inquiry into the mechanisms and treatment of ischemic brain injury. Our investigations, grounded in experimental animal models of cerebral ischemia, have as their ultimate goal the identification of those factors responsible for ischemic injury which may be amenable to therapeutic or prophylactic intervention. The Program Project consists of six investigative proposal together with Core facilities supporting the research program in the areas of brain metabolite analysis, animal physiology, radioisotopic tracer strategies, morphology, computer science/image-processing, and animal behavior. The Cores contribute substantively to the implementation of each Project and unify the Projects by common methodological approaches. Program areas include: (1) treatable mechanisms of brain injury in foal cerebral ischemia; (2) mechanisms of functional recovery following cerebral infarction; (3) an analysis of glutamatergic mediation of ischemic vulnerability; (4) the effect of mild selective cerebral hypothermia in protecting against ischemic brain injury; (5) studies of early indices of cellular damage in the hippocampal slice preparation; and (6) an analysis of local cortical electrophysiological and ion-transport alterations in acute focal cerebral ischemia and their relationship to ultimate tissue injury.